Norris Carly, Murphy Susan F, VandeVord Pamela J
School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA, USA; Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, USA.
Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, USA; Veterans Affairs Medical Center, Salem, VA, USA.
Neurosci Lett. 2025 Feb 6;848:138108. doi: 10.1016/j.neulet.2024.138108. Epub 2024 Dec 27.
Regulation of glutamate through glutamate-glutamine cycling is critical for mediating nervous system plasticity. Blast-induced traumatic brain injury (bTBI) has been linked to glutamate-dependent excitotoxicity, which may be potentiating chronic disorders such as post-traumatic epilepsy. The purpose of this study was to measure changes in the expression of astrocytic and neuronal proteins responsible for glutamatergic regulation at 4-, 12-, and 24 h in the cortex and hippocampus following single blast exposure in a rat model for bTBI. Animals were exposed to a blast with magnitudes ranging from 16 to 20 psi using an Advanced Blast Simulator, and western blotting was performed to compare changes in protein expression between blast and sham groups. Glial fibrillary acidic protein (GFAP) was increased at 24 h, consistent with astrocyte reactivity, yet no other proteins showed significant changes in expression at acute time points following blast (GS, GLT-1, GluN1, GluN2A, GluN2B). Therefore, these glutamate regulators likely do not play a major role in contributing to acute excitotoxicity or glial reactivity when analyzed by whole brain region. Investigation of substructural and subregional effects in future studies, particularly within the hippocampus (e.g., dentate gyrus, CA1, CA2, CA3), may reveal localized changes in expression and/or NMDAR subunit composition capable of potentiating bTBI molecular cascades. Nevertheless, alternative regulators are likely to demonstrate greater sensitivity as acute therapeutic targets contributing to bTBI pathophysiology following single blast exposure.
通过谷氨酸-谷氨酰胺循环对谷氨酸进行调节对于介导神经系统可塑性至关重要。爆炸所致创伤性脑损伤（bTBI）与谷氨酸依赖性兴奋性毒性有关，这可能会加剧诸如创伤后癫痫等慢性疾病。本研究的目的是在大鼠bTBI模型单次爆炸暴露后4小时、12小时和24小时，测量负责谷氨酸能调节的星形胶质细胞和神经元蛋白在皮质和海马中的表达变化。使用先进爆炸模拟器使动物暴露于强度范围为16至20磅力/平方英寸的爆炸中，并进行蛋白质印迹法以比较爆炸组和假手术组之间的蛋白质表达变化。胶质纤维酸性蛋白（GFAP）在24小时时增加，这与星形胶质细胞反应性一致，但在爆炸后的急性时间点没有其他蛋白质显示出表达的显著变化（GS、GLT-1、GluN1、GluN2A、GluN2B）。因此，当通过全脑区域分析时，这些谷氨酸调节剂可能在导致急性兴奋性毒性或胶质细胞反应性方面不发挥主要作用。在未来的研究中，对亚结构和亚区域效应的研究，特别是在海马体（例如齿状回、CA1、CA2、CA3）内的研究，可能会揭示能够增强bTBI分子级联反应的表达和/或NMDAR亚基组成的局部变化。然而，替代调节剂可能作为单次爆炸暴露后导致bTBI病理生理学的急性治疗靶点表现出更高的敏感性。
